Drug Delivery and Translational Research

, Volume 7, Issue 2, pp 228–240 | Cite as

Multi-parametric surface plasmon resonance platform for studying liposome-serum interactions and protein corona formation

  • Otto K. Kari
  • Tatu Rojalin
  • Stefano Salmaso
  • Michela Barattin
  • Hanna Jarva
  • Seppo Meri
  • Marjo Yliperttula
  • Tapani ViitalaEmail author
  • Arto Urtti
Methods Article


When nanocarriers are administered into the blood circulation, a complex biomolecular layer known as the “protein corona” associates with their surface. Although the drivers of corona formation are not known, it is widely accepted that this layer mediates biological interactions of the nanocarrier with its surroundings. Label-free optical methods can be used to study protein corona formation without interfering with its dynamics. We demonstrate the proof-of-concept for a multi-parametric surface plasmon resonance (MP-SPR) technique in monitoring the formation of a protein corona on surface-immobilized liposomes subjected to flowing 100 % human serum. We observed the formation of formulation-dependent “hard” and “soft” coronas with distinct refractive indices, layer thicknesses, and surface mass densities. MP-SPR was also employed to determine the affinity (K D ) of a complement system molecule (C3b) with cationic liposomes with and without polyethylene glycol. Tendency to create a thick corona correlated with a higher affinity of opsonin C3b for the surface. The label-free platform provides a fast and robust preclinical tool for tuning nanocarrier surface architecture and composition to control protein corona formation.


Multi-parametric surface plasmon resonance (MP-SPR) Protein corona Soft corona Liposome Complement system Opsonin 



We are grateful to M.Sc. Tatu Lajunen, B.Sc. Riikka Nurmi, and M.Sc. Antti Louna for the help in preparing and characterizing the control liposome formulations, and to Leena Pietilä and Dr. Mari Palviainen for the help with serum collection and pooling. Liposomes coated with a lipidated oligo-guanidyl derivative were kindly supplied by Professor Stefano Salmaso, University of Padova. Financial support by the Academy of Finland (grants: #137053, #263861, #263567), Tekes—the Finnish Funding Agency for Innovation EV-Extra-Tox project and the Professor Pool—Orion Research Foundation are gratefully acknowledged.

Compliance with ethical standards

All the reported experiments are in compliance with current Finnish law.

Conflict of interest

The authors declare that they have no conflicts of interest. T.R. is affiliated with BioNavis Ltd., Ylöjärvi, Finland.

Supplementary material

13346_2016_320_MOESM1_ESM.docx (21 kb)
ESM 1 (DOCX 20 kb)


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Copyright information

© Controlled Release Society 2016

Authors and Affiliations

  • Otto K. Kari
    • 1
  • Tatu Rojalin
    • 1
  • Stefano Salmaso
    • 2
  • Michela Barattin
    • 2
  • Hanna Jarva
    • 3
  • Seppo Meri
    • 3
  • Marjo Yliperttula
    • 1
    • 2
  • Tapani Viitala
    • 1
    Email author
  • Arto Urtti
    • 1
    • 4
  1. 1.Centre for Drug Research and Division of Pharmaceutical Biosciences, Faculty of PharmacyUniversity of HelsinkiHelsinkiFinland
  2. 2.Department of Pharmaceutical and Pharmacological SciencesUniversity of PadovaPadovaItaly
  3. 3.Department of Bacteriology and Immunology, Immunobiology Research Program, Faculty of Medicine, and HUSLAB, Division of Clinical MicrobiologyHelsinkiFinland
  4. 4.School of PharmacyUniversity of Eastern FinlandKuopioFinland

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